Backgrounds: Functional dyspepsia (FD) is often comorbid with sleep disturbance. The pharmacologic treatments for FD with sleep disturbance have limitations. Transcutaneous auricular vagal nerve stimulation (taVNS) is a new and non-invasive neuromodulation technique and alternative treatment method. However, it is still unclear whether taVNS is effective in treating FD with sleep disturbance. This study aimed to investigate the effects and possible mechanisms of taVNS for patients with FD with sleep disturbance.
Methods: Fifty-four patients with FD and sleep disturbance were randomly divided into the taVNS group (stimulation on the auricular concha) and the transcutaneous non-auricular vagal nerve stimulation (tnVNS) group (stimulation on the auricular scapha). The electrical treatment (25Hz, 2s on, 3s off, 0.5ms, 0.1-9.0mA) persisted 1 hour after lunch and 30 minutes before bedtime each day for 4 weeks. Nepean Dyspepsia Index (NDI), Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) were evaluated before and after treatment. Vagal activity was analyzed by heart rate variability derived from the electrocardiogram (ECG); gastric slow waves and gastric accommodation were assessed with the electrogastrogram (EGG) and nutrient drinking test; and serum melatonin (MT) level was detected by enzyme-linked immunosorbent assay.
Results: 1) Compared with the tnVNS, taVNS decreased the NDI symptom (NDIS) score (30.41±19.19 vs. 49.44±17.91, P<0.001), increased the NDI quality of life (NDIQOL) score (83.50±11.20 vs. 69.66±10.50, P<0.001), and reduced the PSQI score (6.15±3.47 vs. 10.48±3.33, P<0.001) after 4-week treatment. 2) The HAMD (P=0.004) and HAMA (P<0.001) scores with the taVNS treatment were lower than those with the tnVNS treatment. 3) taVNS improved the percentage of normal gastric slow waves (NSW%) in the fasting (P=0.002) and the fed (P<0.001) state, ameliorated the maximum tolerable volume (P=0.043), and increased the serum MT level (P=0.041). 4) The taVNS group had lower low-frequency/high-frequency (LF/HF, P=0.039) and higher HF (P=0.036) in the fasting state than the tnVNS group. 5). Pearson’s correlation analysis of the taVNS group noted that the LF/HF in the fasting state was negatively correlated with the NSW% in the fasting state (r=-0.406, P=0.002) and the serum MT level (r=-0.395, P=0.003).
Conclusions: taVNS ameliorates dyspepsia symptoms and sleep disturbance, as well as anxiety and depression. The outcomes might be attributed to the dual neuromodulating effect of taVNS on both the gut and brain via enhanced vagal activity.
Keywords: Functional dyspepsia; Sleep disturbance; Transcutaneous auricular vagal nerve stimulation; Vagal activity; Melatonin

Yue Zhang

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